Glycogen synthase kinase-3-a new target for lithium's effects in bipolar patients? Academic Article uri icon


  • Eight years ago an editorial entitledLithium Research: State of the Art'(Belmaker and Kofman, 1990) appeared and seemed to narrow down possible heuristic theories of Li action to two sites, inositol monophosphatase and G-proteins. Rapid development of inhibitors of these systems were envisaged that could mimic lithium (Li) and define once and for all the mechanism of Li action. It has been to the surprise of many, therefore, that the Drosophila wingless mutant generated a phenotype similar to Li toxicity, and led to the discovery of Li inhibition of a critical new enzyme. This enzyme therefore is an exciting new candidate for the mechanism of Li action. Li inhibition of glycogen synthase kinase-3 (GSK- 3) occurs at therapeutically relevant concentrations (Ki 1±2 mM; Stambolic et al., 1996; Ki 2.1+ 0.6 mM; Klein and Melton, 1996). GSK-3 is a ubiquitous enzyme, highly abundant in …

publication date

  • January 1, 1998